This invention is generally related to clay-based sorbent compositions and methods for decreasing the bioavailability and toxicity/carcinogenicity of toxins, particularly aflatoxins, in systems by sequestering these agents in the gastrointestinal tract (i.e., enterosoprtion). More specifically, an oral composition is described for use as an enterosorbent therapy to mitigate the adverse effects (both acute and chronic) of aflatoxins in human populations at risk for aflatoxicosis and liver cancer. This enhanced risk is due to frequent and high levels of aflatoxin exposure in the diet. The composition contains an effective amount of a processed calcium aluminosilicate clay in a powder form. This processed calcium aluminosilicate clay possesses less than the tolerable daily human intake of tetrachlorodibenzo-p-dioxin (TCDD) and priority toxic metal contamination based on EPA, JECFA and WHO recommendations. The compositions and methods are used as part of an oral treatment. Additionally, the clay of this invention does not interfere with the treated system's or medium's utilization of important vitamins and other micronutrients that are found naturally in the diet. The processed clay of this invention binds aflatoxins preferentially, with high affinity and high capacity in the gastrointestinal tract, resulting in a notable reduction in exposure (based on aflatoxin-specific biomarkers). Decreased exposure to aflatoxins from contaminated diets could reduce the risk of disease and death from these poisons.
Aflatoxins
Introduction:
Concerns about the quality and safety of foods destined for animal and human consumption have evoked a growing awareness of the significant hazards associated with chemicals known as the aflatoxins. In historical context, the aflatoxin problem in foods is longstanding, unavoidable and seemingly inextricable. Aflatoxins (Afs) are harmful by-products of mold growth and are potentially fatal to humans and animals. Importantly, the aflatoxins are heat stable, survive a variety of food processing procedures, and occur as contaminants of most foods (particularly those derived from maize and peanuts). Aflatoxin B1 (AfB1), the most toxic of four naturally occurring aflatoxins (FIG. 1), is a direct acting mutagen and has been shown to disrupt genes involved in carcinogenesis and tumor suppression. It reacts in vivo with DNA to give trans-8,9-dihydro-8-(N7-quanyl)-9-hydroxy-aflatoxin B1 as the primary aflatoxin-DNA adduct. Along with hepatitis B virus infection, it has been implicated as a factor in the etiology of hepatocellular carcinoma (HCC). Aflatoxin B1 has also been shown to be immunotoxic and antinutritional. In the U.S., the action level for Afs in foods intended for human consumption has been set to 20 ppb. A recent outbreak of aflatoxin poisoning in Kenya was linked to consumption of foods containing levels as high as 8,000 ppb, indicating a critical need for treatment regimens to alleviate acute aflatoxicosis in populations at high risk for aflatoxicosis.
Occurrence:
Drought is a common cause of fungal infection and enhanced production of aflatoxins. This is especially true in developing countries (40° N and S of the equator), where aflatoxins in the diet of humans and animals are largely uncontrolled. The problem impacts the poorest people, who are most likely to consume foods contaminated with aflatoxins and suffer the consequences, including disease and acute death. Thus, dietary interventions and therapies to alleviate aflatoxicosis in humans and animals are high priorities; the use of dietary montmorillonite clay as an aflatoxin enterosorbent, may provide a practical and cost-effective approach to the problem.
Chemopreventive Strategies that Modulate the Metabolism of Aflatoxin:
Avoiding consumption of aflatoxin contaminated foods can significantly reduce the risk of acute or chronic aflatoxicosis in systems, mediums, or subjects; however, in developing countries, a change in the diet is usually not feasible. One approach to the problem is the strategy of chemoprevention in high-risk populations. This strategy involves the use of natural or synthetic agents to block, retard, reverse or modulate the carcinogenic process. Many chemopreventive agents have been studied and some exist as natural constituents in the human diet such as those found in fruits and vegetables. Several of these have shown efficacy in protection against a wide range of carcinogens; however, most occur at very low levels in a nutritionally balanced diet and they are poorly absorbed in the gastrointestinal tract. Studies have investigated the use of the antischistosomal drug oltipraz as a chemopreventive agent in systems or subjects exposed to dietary aflatoxins in China. In clinical trials, researchers have demonstrated that oltipraz increases the level of glutathione S-transferase mediated conjugation of aflatoxin 8,9-epoxide and also results in the inhibition of cytochrome P450 1A2 activity. Other work has shown that oltipraz may also inhibit hepatitis B virus (HBV) transcription through elevation of p53 providing an additional contribution to HCC chemoprevention. Natural products such as chlorophyllin may also be used to sorb aflatoxins and reduce the amount of toxin reaching the liver. Chlorophyllins are constituents of the human diet that have been found to be effective anti-carcinogens in several animal models. Chlorophyllin is thought to enhance metabolism and act as an interceptor molecule by binding with carcinogens, such as AfB1 thereby diminishing bioavailability. In a clinical trial in China, participants were randomly assigned to two groups, which were given 100 mg of chlorophyllin or a placebo three times a day for four months. Chlorophyllin consumption at each meal led to an overall 55% reduction in median urinary levels of aflatoxin-N7-guanine adducts compared with consumption of the placebo (Egner et al., 2001). The extended use of these compounds in humans would require careful evaluation including long-term effects of enzyme modulation and potential interferences with the uptake of essential nutrients from the diet. Green-tea derived polyphenols are also under investigation as possible interventions for populations at high risk for HCC. These compounds are highly effective chemopreventive agents against cancer at different organ sites in various animal models. Research has indicated that green tea inhibits the initiation of AfB1-induced hepatocarcinogenesis in the rat by modulation of AfB1 metabolism. Additional studies with B6C3F1 mice have shown that the administration of green tea (3% in water) prevented the hepatic focal lesion growth induced by dieldrin. Green tea co-treatment also resulted in an increase in the apoptotic index in mouse liver focal lesions. In humans, inverse associations between the level of green-tea consumption and the risk of development and/or time of cancer onset have also been observed.
Dietary Clay Interventions that Reduce the Bioavailability of Aflatoxins:
The consumption of clays (geophagy) has been recorded from traditional human societies for centuries and is “culturally acceptable” in Africa and China. Using multiple animal models, our laboratory has shown that calcium montmorillonite clays can be effective in preventing the adverse effects of dietary aflatoxins. The strategy of reducing foodborne exposure to mycotoxins via the inclusion of various binding agents or sorbents in the diet has been given considerable attention. As early as 1979, adsorbent clay minerals were reported to bind aflatoxin B1 in liquids. Also, bleaching clays, that had been used to process canola oil, were found to lessen the effects of T-2 toxin.
HSCAS Enterosorbent Interventions for Aflatoxins in the Diet:
In the first enterosorbent study with aflatoxins, HSCAS (HSCAS™), a calcium montmorillonite clay that is sold as an anticaking additive for animal feeds, was reported to sorb aflatoxin B1 with high affinity and high capacity in aqueous solutions and rescued broiler and Leghorn chicks from the toxic effects of 7,500 ppb of aflatoxin in the diet. Since these early studies, HSCAS and other similar montmorillonite and bentonite clays have been reported to diminish the effects of aflatoxins in a variety of young animals including rodents, chicks, turkey poults, ducklings, lambs, pigs, mink and trout. HSCAS has also been shown to decrease the bioavailability of radiolabeled aflatoxins and reduce aflatoxin residues in poultry, rats and pigs (FIG. 2). Levels of aflatoxin M1 in milk from lactating dairy cattle and goats were also diminished with the inclusion of HSCAS in the diet.
Molecular Mechanisms and Thermodynamics for the Sorption of Aflatoxins to HSCAS:
Insight into the adsorption of AfB1, onto the surfaces of HSCAS came from the observation that stereochemical differences between some of the aflatoxin analogs resulted in a significant effect on the tightness of binding (even though the carbonyl functional groups were identical). These results also suggested that the molecular mechanism for the adsorption of aflatoxins onto HSCAS may favor an optimal orientation where the furan is aligned away from the surface. AfB1 is strongly bound to HSCAS based on the thermodynamics of the sorption and an estimated heat of sorption (enthalpy) of −40 kJ/mol. A potential chemical reaction that may explain these results is an electron donor acceptor (EDA) mechanism. This mechanism involves sharing of electrons from the negative surface of the clay with atoms in the adsorbed molecule that are partially positive. The carbons comprising the dicarbonyl system in aflatoxins are partially positive (electron poor) and have also been shown to be essential to the adsorption process. When the summation of partial charges of the carbons of the carbonyl functional groups for each ligand was plotted versus binding strength, there was a significant correlation. When the ligands that were not planar on the side of the molecule opposite the dihydrofuran functional group were removed from the set of test compounds, the correlation was significantly improved. Interference from compounds with stereochemical restrictive groups could also play an important role in the adsorption process. For the analogs that contain functional groups that make them larger than AfB1, their insertion, docking and adsorption at clay surfaces, separating interlayer channels, might be restricted.
Specificity of HSCAS for Aflatoxins:
Research has supported the conclusions that HSCAS has a notable preference (and capacity) for the aflatoxins at levels in the diet at, or below, 0.5% w/w (the level that is recommended for anticaking activity in animals feeds). For example, HSCAS at a level of 0.5% in the diet of poultry, did not impair phytate or inorganic phosphorous utilization. In other poultry nutrition studies, the addition of HSCAS at concentrations of 0.5% did not impair the utilization of riboflavin, vitamin A, manganese, or zinc. Also, in earlier studies, HSCAS (at an inclusion rate of 0.5%) has been shown to protect young chickens from very high levels of aflatoxins (i.e., 7,500 ppb). While clay-based interventions are clearly effective for aflatoxins, an analogous technology is not yet available for other important mycotoxins. For the most part, unmodified NS clays do not “tightly” bind other structurally diverse mycotoxins, e.g., zearalenone, deoxynivalenol, T-2 toxin, ochratoxin A, cyclopiazonic acid, ergotamine, and fumonisins, nor do they significantly prevent the adverse effects of these mycotoxins when included in the diet of animals. For example, in enterosorbent studies in poultry with mycotoxins (other than the aflatoxins), the inclusion of HSCAS in the diet did not significantly prevent the adverse effects of cyclopiazonic acid, T-2 toxin, diacetoxyscirpenol, ochratoxin A, and fumonisins. The use of clay in mink fed zearalenone helped to alleviate some fetotoxicity but did not reduce the hyperestrogenic effects. Also, the addition of clay at 0.5 and 1.0% w/w in the diet, did not influence the average daily weight gain of pigs exposed to deoxynivalenol. The only effective method for decreasing the toxicity of deoxynivalenol in this study was the dilution of the contaminated maize with uncontaminated maize. The possibility of supplementing livestock diets with HSCAS to prevent fescue toxicity has also been investigated. Although in vitro experiments predicted good binding of ergotamine to montmorillonite clays in aqueous solution, HSCAS (at levels of 2.0% by weight) did not protect rats or sheep from fescue toxicosis. In order to further confirm the specificity of HSCAS for AfB1, protocols were developed to nanostructure thin films of the HSCAS onto the surface of quartz and use the resulting composite as an affinity probe for aflatoxins in contaminated media. Our findings suggested that this composite media (when packed in small glass cleanup columns) was comparable in selectivity to the Aflatest affinity column from VICAM.
Chronic Animal Study with HSCAS:
In initial short-term animal studies with HSCAS, no observable adverse effects were reported following ingestion of clay in the diets. A more recent study in which Sprague-Dawley (S-D) rats ingested HSCAS at dietary concentrations as high as 2.0% throughout pregnancy showed neither maternal nor fetal toxicity, and also did not show significant trace metal bioavailability in a variety of tissues. A rodent model was also used to evaluate the relative safety of chronic exposure to HSCAS via the diet. The study involved male and female Sprague-Dawley rats which were fed rations containing 0, 0.25, 0.5, 1.0, and 2.0% levels of NS clay ad libitum over a 6.5-month period. The results of this study indicated that rats treated with 0.25-2% NS clay in the diet did not exhibit dose-dependent or HSCAS-related adverse effects on body weight gains, feed conversion ratios, relative organ weights, gross anatomy and histological appearance of major organs; hematology, and serum biochemistry parameters. Additionally, levels of selected essential nutrients including vitamins A and E, Fe, and Zn were unaffected. These findings suggested that enterosorbent therapy or dietary intervention with HSCAS may be a potential option for the management of aflatoxicoses in high-risk human populations.
Adverse Events Trial with HSCAS in Systems or Subjects:
Following the chronic rodent study, a two-week short-term safety evaluation of HSCAS was carried out in healthy human volunteers. This phase I Adverse Events trial was designed to determine short term safety and tolerance of HSCAS in subjects. Prior to encapsulation, HSCAS was analyzed for concentrations of various environmental contaminants, including dioxins/furans and heavy metals to insure compliance with federal and international standards (Table 1). For example, the amount of heavy metal contamination in a derived dose of HSCAS is less than the Joint FAO/WHO Expert Commission on Food Additives (JECFA) criteria. More specifically, a derived dose equal to 3 g of HSCAS/day for Co, Cr, Zn, Mo, Se, Ni, Hg, Pb, Cd, As, and dioxins (TCDD and OCDD) is below JECFA criteria.
HSCAS was sterilized at 121° C. prior to packaging into capsules. The HSCAS capsules were produced under sterile conditions using U.S. Good Manufacturing Practices. In the human study, the overall design followed the guidelines for a randomized and double blinded phase I clinical trial. A total of 50 adults who met the recruiting standards were voluntarily enrolled in the study. They were randomly divided into two study groups. The low dose group took three capsules of HSCAS (0.5 g) three times a day for two weeks. The high-dose group took three capsules of HSCAS (1.0 g) three times a day for two weeks. All capsules were of the same color and size. The two dose levels were extrapolated from previously published animal studies. Results indicated that both doses of HSCAS used in this study were tolerable for all study participants. Gastrointestinal adverse effects were noticed in some subjects, 24% ( 6/25) in the 1.5 g group and 28% ( 7/25) in the 3.0 g group. Symptoms included bloating, constipation, diarrhea, flatulence, and abdominal discomfort. Two participants in the low-dose (1.5 g HSCAS) group reported experiencing some degree of dizziness, an effect which was not evident in the high-dose (3.0 g NS) group. All symptoms described were recorded in the first 2-days after taking the NS capsules and no symptoms (or complaints) were recorded thereafter. All side-effects reported, except from one participant, were assessed to be mild, and no significant difference between the two treatment groups was observed. Results of this study showed that administration of HSCAS capsules at 1.5-3.0 g/day to healthy human subjects for 14 days was relatively safe, as demonstrated by the analysis of biochemical and hematological parameters, as well as physical examinations. It has been postulated that some clay minerals may sorb vitamins; however, in this study no statistical differences were observed in the levels of serum vitamins A and E after treatment with either dose of HSCAS. This evidence further confirms that HSCAS demonstrates binding specificity for AFs and lack of interaction with vitamins A and E. No significant differences were found in levels of the majority of minerals analyzed, with two exceptions: lower inorganic sulfur concentration in the low-dose group and higher strontium concentrations in both groups. The clinical significance of these findings is not yet known and will be monitored in future intervention studies.
Aflatoxin Carcinogenicity:
Human hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and the leading cause of death in parts of China and Africa, where chronic infection with hepatitis B virus (HBV) and exposure to aflatoxins in the diet are considered the main etiological factors. In more developed countries, adequate food supplies combined with regulations that monitor these aflatoxin levels in foods, offer a means of protection and reduced exposure in human populations. In countries where starvation is endemic and food quality regulations are unavailable, daily exposure to aflatoxins substantially increases the risk of HCC and other adverse human health effects. In many of these cases disposal and/or substitution of mycotoxin-contaminated foodstuffs is not a viable option. Unfortunately, such realities of life still exist in the 21st century and highlight the importance of reducing or eliminating the dietary exposure to aflatoxins in order to improve the health status and quality of life in these high-risk human populations. Aflatoxins are difuranocoumarin derivatives produced by many strains of Aspergillus flavus and Aspergillus parasiticus; in particular, A. flavus is a common contaminant in agriculture. These toxigenic fungal species are distributed throughout the world, and are more prevalent in warm, sub-tropical and tropical climates in comparison with temperate environments. Natural contamination of cereal grains, oilseeds, nuts, fruits, tobacco, and a wide range of other commodities is a common occurrence. Of the four major aflatoxin congeners produced by Aspergillus sp., (B1, B2, G1, and G2), aflatoxin B1 (AfB1) is the most potent hepatocarcinogen and has the greatest human health significance. The liver is the primary site of biotransformation of ingested aflatoxins. Initially, AfB1 undergoes an oxidation by cytochrome P450 CYP1A2 and CYP3A4, yielding two aflatoxin-8,9-epoxide stereoisomers. The exo epoxide, a highly reactive intermediate, reacts with the N7 atom of guanine to form a promutagenic DNA adduct, AfB1—N7-guanine. This aflatoxin-DNA adduct is unstable and undergoes depurination leading to its excretion in urine. The exo epoxide is also capable of binding to lysine residues in serum albumin, as well as other cellular proteins. CYP1A2 also catalyzes the hydroxylation of AfB1 to yield AfM1, which is a major aflatoxin metabolite in humans and other oxidation products such as AfP1, and AfQ1. These metabolites can be excreted without further biotransformation or they can be conjugated by UDP-glucuronosyl transferases, however, AfM1 is not a substrate for glucuronidation. The aflatoxin-8,9-epoxide intermediate is also a substrate for glutathione-5-transferases, which produce a stable, nontoxic, polar product excreted in the bile. The aflatoxin-glutathione product undergoes further sequential metabolism in the liver and kidneys to be excreted as a mercapturic acid (aflatoxin-N-acetylcysteine) in the urine. Aflatoxin was initially classified as a human carcinogen by the International Agency on Research in Cancer in 1993, and further epidemiological and experimental research continues to provide evidence of a strong link between aflatoxin exposure and HCC. In the Peoples Republic of China alone, HCC accounts for more than 200,000 deaths annually and is the third leading cause of cancer mortality. In particular, HCC is the leading cause of cancer death in Qidong, a city in eastern Jiangsu Province, People's Republic of China, and accounts for up to 10% of all adult deaths in some of the rural townships. Early evidence associating aflatoxin exposure to HCC was based largely on estimates of aflatoxin ingestion as measured in contaminated food or from dietary questionnaires. Further studies have relied on the measurement of various biomarkers in the urine and blood as a more accurate means of correlating aflatoxin exposure with the occurrence of HCC. The urinary AFB—N7 guanine adduct has been used in many AfB1 studies in mediums, systems, or subjects, as a quantitative indicator of exposure to aflatoxin. AfM1 is a major urinary metabolite excreted following AfB1 ingestion and may also be used as a linear biomarker of aflatoxin exposure. In addition, the aflatoxin-albumin adduct in serum has been used for longer term exposure estimates. The availability and application of these aflatoxin-specific biomarkers has helped to better characterize human exposure and susceptibility to aflatoxins in high risk populations. For example, nested case-control biomarker studies conducted in Shanghai in the early 1990s showed a significant link between aflatoxin exposure and HCC as well as a dramatic sixty-fold increase in the risk of liver cancer when aflatoxin exposure was concomitant with chronic hepatitis B infection. Subsequent studies in Taiwan and Qidong have confirmed these findings.
U.S. Pat. No. 5,178,832, issued to Phillips, et al., on Jan. 12, 1993, and titled “Selective Immobilization and Detection of Mycotoxins in Solution” describes how certain minerals, particularly various naturally occurring forms of aluminum oxide, will preferentially bind selective mycotoxins from a mixture of mycotoxins. These adsorbents, when used in various combinations and/or in conjunction with the adsorbents of the prior art, permit the construction of detector tubes which can resolve mycotoxins in solution and provide a semi-quantitative fluorescent determination of their concentration in feed or foodstuff samples. The detector tubes comprise transparent tubes packed with isolated layers of selected minerals. A solvent extract from a sample potentially contaminated with mycotoxins is passed through the column. As the mycotoxin mixture passes through the detector tube and is contacted by the various mineral adsorbents, selected mycotoxins are immobilized on a specific mineral while other mycotoxins and co-extracted organic compounds pass through that layer to be immobilized on subsequent downstream mineral layers. The presence of mycotoxins is determined by examining the developed detector tube under a long wave UV light source.
U.S. Pat. No. 5,165,946 issued to Taylor, et al., on Nov. 24, 1992, titled “Animal Feed Additive and Method for Inactivating Mycotoxins Present in Animal Feeds,” describes a dry solid animal feed composition capable of inactivating mycotoxins. When feed was contaminated with mycotoxin and was admixed with a mycotoxin inactivating agent comprising particles of a phyllosilicate mineral capable of inactivating mycotoxins, the composite material enhanced the mycotoxin inactivating capacity of the phyllosilicate.
Clay as a Treatment for Aflatoxins.
The clay-based composition of this invention can be used to bind and treat exposure to environmental toxins, treat acute aflatoxin poisoning and prevent aflatoxin induced liver cancer and chronic aflatoxicosis. However, one of ordinary skill in the art will recognize that there are many different types of clay, and clay uses and applications have been well-documented throughout human history.
Clay is a generic term for an aggregate of hydrous silicate particles. Generally, clay consists of a variety of phyllosilicate minerals generally rich in silicon and aluminium oxides, and hydroxides. Clays are distinguished from other small particles present in soils such as silt by their small size, flake or layered shape, affinity for water and high plasticity index. Main groups of phyllosilicate clays include kaolinite, montmorillonite-smectite, illite, and chlorite.
Montmorillonite clay is typically formed as a weathering product of low silica rocks. Montmorillonite is a member of the smectite group and a major component of bentonite.
Varve (or varved clay) is clay with visible annual layers, formed by seasonal differences in erosion and organic content. This type of deposit is common in former glacial lakes from the ice age.
Quick clay is a unique type of marine clay, indigenous to the glaciated terrains of Norway, Canada, and Sweden. It is a highly sensitive clay, prone to liquefaction which has been involved in several deadly landslides.
Other names for clay include: HSCAS, Akipula, aluminium silicate, anhydrous aluminum silicates, askipula, beidellitic montmorillonite, benditos, bioelectrical minerals, cipula, chalk, clay dirt, clay dust, clay lozenges, clay suspension products, clay tablets, colloidal minerals, colloidal trace minerals, fossil farina, humic shale, Indian healing clay, kaolin, kipula, mountain meal, panito del sensor, plant-derived liquid minerals, tirra santa, Terra sigillata, white clay, white mud, etc.
Medicinal Uses of Clay.
Today, clay is used in many industrial processes to make bricks, cooking pots, art objects, dishware, sparkplug bodies, cement production and chemical filtering. According to folklore, eating clay has many medicinal purposes, but the scientific literature indicates that ingesting certain clays may be harmful to the consumer. The chemical nature of clays may allow them to sorb a variety of potentially detrimental agents. For example, clay pots containing candy (Jarritos brand Tamarindo candy) have been recalled in the United States by the Food and Drug Administration due to high levels of lead in the candy that was derived from the clay pots. Clay products may contain varying amounts of aluminum, arsenic, barium, lead, nickel, titanium and other trace metals. Additionally, elevated levels of 2,3,7,8-tetracholorodibenzo-p-dioxin have been found in farm-raised catfish and eggs from chickens fed a diet including ball clay from a mine in Mississippi. Additionally, chronic clay eating may be associated with trace element deficiency. However, it should be pointed out that the group of clays used predominantly in the ceramics industry and consumed by systems or subjects are the kaolinites (Ball clays).
Therefore, clays (especially kaolinites) that are ingested by humans should not have elevated levels of toxic agents. The processed clay of this invention can be used to treat or prevent aflatoxin toxicity. Although clay has been used medicinally for centuries in Africa, India, and China, and by Native American groups, one of ordinary skill in the art understands there is a potential for severe adverse effects with chronic oral ingestion of certain clays. As described below, the scientific and medical communities believe these adverse effects may outweigh any potential benefits.
The practice of eating dirt, clay, or other non-nutritious substances may be referred to as “pica” or “geophagia,” and is common in early childhood and in mentally handicapped or psychotic patients. There is some evidence that mineral deficiencies such as iron deficiency may lead to pica, and prevalence is higher in developing countries and in poor communities. Chronic clay ingestion may lead to iron malabsorption and further precipitate this condition. There is insufficient scientific evidence to recommend for or against the use of clay for any medical condition. The potential for adverse effects with chronic oral ingestion of clay may outweigh any potential benefits.
Clay products may contain varying amounts of aluminum, arsenic, barium, lead, nickel, titanium and other trace metals. Certain colloidal mineral supplements may also contain unsafe concentrations of radioactive metals. Ingestion of certain clays is possibly unsafe when used in patients during pregnancy or lactation, or when used in children. Some clays may possess potassium-binding capacity, and chronic ingestion of these clays has been associated with severe hypokalemia, particularly in patients with renal insufficiency. It has been suggested that habitual eating of kaolinic clays (pica or geophagia) may lead to iron malabsorption and severe deficiency, and may be associated with anemia and lead poisoning.
The following physiological problems have reported with “pica” or “geophagia:”
Allergy/hypersensitivity to certain clay, can be characterized by an edematous appearance, dilated cardiomyopathy, polyuria, and death. Additionally, skin dryness, skin ulcerations were noted over the upper and lower extremities of subjects.
Neurologic/CNS:
Pica has been associated with the development of lead poisoning in children, and may carry a risk of central nervous system damage. In one case report, a 6-year-old girl died from complications of lead poisoning and encephalopathy after ingesting lemonade from a glazed clay pitcher. The risk of neurolathyrism, a neurodegenerative, irreversible disorder that cause spastic paraparesis of the body that leads to paralysis, was reported to quadruple in a case-control study in Ethiopia when cooking grass pea with clay utensils.
Psychiatric:
Habitual pica may occur in patients with mental illness, including psychotic disorders.
Pulmonary/Respiratory:
In the 1960s, it was reported that children with a history of pica were predisposed to develop more frequent and severe respiratory infections than healthy children. Chronic bronchitis, dyspnea, and pneumoconiosis have been associated with dust exposure in the heavy clay industry.
Cardiovascular:
Pica was reported to be associated with dilated cardiomyopathy and death.
Gastrointestinal:
Clay eating may precipitate constipation or diarrhea. Heartburn, flatulence, loss of appetite, and vomiting after meals have also been reported. Clay eating has also been associated with intestinal obstruction and necrotizing enteritis, leading to bowel perforation. Colonic stones have been reported in two children with pica. Geophagia has been associated with hepatosplenomegaly.
Renal:
Clay possesses potassium-binding capacity, and chronic clay ingestion has been associated with severe hypokalemia, particularly in patients with renal insufficiency, but not in those receiving hemodialysis.
Endocrine:
Myopathy due to severe hypokalemia has been reported in I case report with large quantities of clay ingestion.
Genitourinary:
Chronic clay eating has been associated with polyuria and urge incontinence, as well as hypogonadism.
Hematologic:
Pica may lead to iron malabsorption and severe deficiency, and has been associated with anemia.
Musculoskeletal:
Myositis has been associated with chronic clay ingestion. Myopathy due to severe hypokalemia has been reported with large quantities of clay ingestion.
Infectious Disease:
Hookworm infections have been associated with ingestion of clay. Tetanus contracted from clay has been described in an infant who ate clay, and in a newborn whose umbilical cord was wrapped in clay.
Iron, Calcium, Magnesium:
Certain clay may act as a cation exchange resin. Calcium and magnesium in these clays can be exchanged with iron, making iron unavailable because of formation of insoluble iron complexes. Iron deficiency may result, and levels of calcium or magnesium may increase.
Potassium:
Certain clays possess potassium-binding capacity, and have been associated with hypokalemia.
One of ordinary skill in the art understands that there is insufficient scientific and clinical evidence in the literature to recommend for or against the medicinal use of certain clays, however, the current illustrations in medicine tend to teach away from using clay as a safe treatment in patients with aflatoxin poisoning, or liver cancer in predisposed subjects. The methods and compositions of this invention utilize isolated clay compositions that are not typically consumed by systems/subjects or used in the manufacture of ceramic eating and drinking utensils. The processed clay of this invention has a particular chemical makeup that does NOT impart adverse health effects when administered orally (based on extensive scientific studies in humans and animals).